The pharmaceutical compounds which are the subject of the formulation described in the present invention are included in European Patent Application EP 134,124, which is included in the present application by reference.
These compounds, and still more specifically the following compound whose international name is ebastine or 4-diphenylmethoxy-1-[3-(4-tert-butylbenzoyl)propyl]piperidine of formula: ##STR1## are not water-soluble. It is therefore difficult to put them into an aqueous pharmaceutical dosage form such as a syrup.
The salt formed between the above compound and lactic acid has its solubility optimum at pH 2, this solubility in any case being limited to 0.8 mg/ml, but it displays optimal stability only at pH 4. Thus, the pH values of optimal solubility and of optimal stability can in no case enable stable solutions of ebastine having a minimal concentration of 1 mg/ml to be obtained.
These compounds have antihistaminic H.sub.1 activity, and are useful in the treatment of respiratory, allergic or cardiovascular disorders. Thus, they relax vascular and bronchial smooth muscle in vitro and in vivo.
They also inhibit the constricting effect of adrenaline and of potassium ions at both intestinal level and tracheal level. Thus, they block bronchoconstriction caused by histamine aerosols at doses as low as 1 mg/kg.
These compounds are active when administered parentorally and also when administered orally. When they are administered orally, it is necessary to use a salt of the carboxylic acid, the solubility of which in water is always low. Thus, in the patent application cited above, that is to say European Patent Application EP 134,124, Example 7, it was necessary, in order to form a solution, to add to the active principle described above, in its acid form, an emulsifier such as hydrogenated and ethoxylated castor oil, better known under the trade name Cremophor, at doses which are far from negligible since they are in the region of 2% by weight relative to the final solution, which represents a quantity of emulsifier equal to four times the quantity of active principle.
Now, it is always difficult in the pharmaceutical industry to offer on the market a solution which has the appearance of a soapy solution rather than that of a syrup. We hence sought to avoid the use of any emulsifier in our formulation. The emulsifier used in the composition of Patent EP 134,124 has, in addition, two major drawbacks: it has a taste which does not permit satisfactory flavoring to be obtained, and it causes intolerance phenomena resulting in vomiting of the medicament.